Engineering nanomaterials for glioblastoma nanovaccination

Glioblastoma is a lethal brain cancer with treatment resistance stemming from its interactions with the surrounding microenvironment and obstacles such as the blood–brain barrier. Conventional therapies such as surgery and chemotherapy have shown limited efficacy, whereas immunotherapies, effective in other solid cancers, face obstacles in glioblastoma owing to its unique immunological dysfunction. Despite the development of peptide, neoantigen, cell-based and mRNA-based vaccines, progress to advanced clinical trials has been sluggish. Factors contributing to this slow progress include the immunosuppressive microenvironment of the tumour, the presence of the blood–brain barrier and the inherent instability of glioblastoma vaccines, collectively hindering treatment efficacy. In this context, nanomaterials have emerged as promising owing to their capacity to cross the blood–brain barrier, shield therapeutics from degradation and efficiently target the brain. In this Perspective, we highlight the development of glioblastoma nanovaccination, discussing strategies for nanoparticle engineering to breach the blood–brain barrier and target both immune and glioblastoma cells, paving the way for potential breakthroughs in glioblastoma treatment.